Human ocular-derived virus-specific CD4+ T cells control varicella zoster virus replication in human retinal pigment epithelial cells.
OBJECTIVE
Varicella zoster virus (VZV)-induced retinitis is characterized by the presence of virus-infected cells in the retinal layer and the ocular infiltration of VZV-specific T cells. Herein, the susceptibility of human retinal pigment epithelial (RPE) cells to VZV infection and the ability of virus-specific CD4(+) T cells to control VZV infection in RPE cells in vitro is addressed.


METHODS
Human primary RPE cell cultures (n=2) were infected with a VZV strain expressing green fluorescent protein. The infection and viability of infected RPE cells was monitored by flow cytometry or by a fluorescent imager on RPE monolayers. RPE cells, pretreated with or without interferon-gamma (IFN-gamma), were infected with VZV and subsequently cultured with VZV-specific CD4(+) T-cell clones (TCCs; n=3) recognizing disparate VZV proteins presented by different HLA class II alleles. IFN-gamma production and cytotoxicity of the TCCs in response to VZV-infected RPE cells was determined by flow cytometry.


RESULTS
Human RPE cells are permissive to a productive VZV infection. VZV-infected RPE cells presented the cognate antigen to the CD4(+) TCCs only if the RPE cells were pretreated with IFN-gamma and expressed the appropriate HLA class II allele. VZV-specific TCCs inhibited productive VZV infection in RPE cells, which was in part attributed to TCC-mediated killing of the VZV-infected RPE cells.


CONCLUSIONS
The results presented suggest that RPE cells may play a role as retina-resident antigen-presenting cells in the intraocular, VZV-specific, T cell-mediated inflammatory response of VZV-induced uveitis.
Milikan
Johannes C M
JC
Institute of Virology, Erasmus Medical Center, Rotterdam, The Netherlands.
Baarsma
G Seerp
GS
Kuijpers
Robert W A M
RW
Osterhaus
Albert D M E
AD
Verjans
Georges M G M
GM
D000938:Antigen-Presenting Cells / Q000502:physiology; D015703:Antigens, CD / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006563:Herpes Zoster Ophthalmicus / Q000276:immunology*; D014645:Herpesvirus 3, Human / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000821:virology*; D012173:Retinitis / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology; D014779:Virus Replication
D015703:Antigens, CD; D000949:Histocompatibility Antigens Class II; D014764:Viral Proteins; D049452:Green Fluorescent Proteins; D007371:Interferon-gamma